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Protein

Ras association domain-containing protein 5

Gene

RASSF5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Potential tumor suppressor. Seems to be involved in lymphocyte adhesion by linking RAP1A activation upon T-cell receptor or chemokine stimulation to integrin activation. Isoform 2 stimulates lymphocyte polarization and the patch-like distribution of ITGAL/LFA-1, resulting in an enhanced adhesion to ICAM1. Together with RAP1A may participate in regulation of microtubule growth. The association of isoform 2 with activated RAP1A is required for directional movement of endothelial cells during wound healing. May be involved in regulation of Ras apoptotic function. The RASSF5-STK4/MST1 complex may mediate HRAS and KRAS induced apoptosis.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri122 – 170Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST49

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ8WWW0.
SIGNORiQ8WWW0.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras association domain-containing protein 5
Alternative name(s):
New ras effector 1
Regulator for cell adhesion and polarization enriched in lymphoid tissues
Short name:
RAPL
Gene namesi
Name:RASSF5
Synonyms:NORE1, RAPL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:17609. RASSF5.

Subcellular locationi

  • Cytoplasm
  • Cytoplasmcytoskeleton

  • Note: Isoform 2 is mainly located in the perinuclear region of unstimulated primary T-cells. Upon stimulation translocates to the leading edge and colocalizes with ITGAL/LFA-1 in the peripheral zone of the immunological synapse. Isoform 2 is localized to growing microtubules in vascular endothelial cells and is dissociated from microtubules by activated RAP1A.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Microtubule

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi83593.
OpenTargetsiENSG00000266094.
PharmGKBiPA134958571.

Polymorphism and mutation databases

BioMutaiRASSF5.
DMDMi74751587.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002404011 – 418Ras association domain-containing protein 5Add BLAST418
Isoform 2 (identifier: Q8WWW0-2)
Initiator methionineiRemovedCombined sources

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei182PhosphoserineBy similarity1
Modified residuei279PhosphoserineCombined sources1
Modified residuei352PhosphothreonineCombined sources1
Isoform 2 (identifier: Q8WWW0-2)
Modified residuei2N-acetylthreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ8WWW0.
MaxQBiQ8WWW0.
PaxDbiQ8WWW0.
PeptideAtlasiQ8WWW0.
PRIDEiQ8WWW0.

PTM databases

iPTMnetiQ8WWW0.
PhosphoSitePlusiQ8WWW0.

Expressioni

Tissue specificityi

Widely expressed. Frequently down-regulated in lung tumor cell lines and primary lung tumors.2 Publications

Gene expression databases

BgeeiENSG00000136653.
CleanExiHS_RASSF5.
ExpressionAtlasiQ8WWW0. baseline and differential.
GenevisibleiQ8WWW0. HS.

Interactioni

Subunit structurei

Interacts directly with activated HRAS; a RASSF5-STK4/MST1 complex probably associates with activated HRAS. Interacts with KRAS. Probably interacts with Ras-like GTPases RRAS, RRAS2, MRAS, RAP1B, RAP2A and RALA. Can self-associate. Interacts with RSSF1 isoform A. The RSSF1 isoform A-RSSF5 heterodimer probably mediates the association of RSSF1 with HRAS (By similarity). Isoform 2 interacts with activated RAP1A and ITGAL/LFA-1. Binds STK4/MST1, inhibiting STK4/MST1 autoactivation.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
A8K9403EBI-367390,EBI-10174788
AMOTL2Q9Y2J4-43EBI-367390,EBI-10187270
BTRCQ9Y2973EBI-367390,EBI-307461
GABARAPO951662EBI-367390,EBI-712001
GABARAPL1Q9H0R82EBI-367390,EBI-746969
GABARAPL2P605202EBI-367390,EBI-720116
HRASP011122EBI-367390,EBI-350145
KRT40Q6A1623EBI-367390,EBI-10171697
KRTAP4-2Q9BYR53EBI-367390,EBI-10172511
MAP1LC3BQ9GZQ85EBI-367390,EBI-373144
MAP1LC3CQ9BXW42EBI-367390,EBI-2603996
MYLIPQ8WY643EBI-367390,EBI-6952711
RABIFP472243EBI-367390,EBI-713992
RAP1AP628343EBI-960502,EBI-491414
RAP1BP612243EBI-367390,EBI-358143
RAP2BP612253EBI-367390,EBI-750871
RASSF2P507493EBI-367390,EBI-960081
RELQ048643EBI-367390,EBI-307352
SMAD4Q134853EBI-367390,EBI-347263
STK3Q131887EBI-367390,EBI-992580
STK4Q130437EBI-367390,EBI-367376
TRAF1Q130773EBI-367390,EBI-359224
TRAF2Q129333EBI-367390,EBI-355744
VPS28Q548N13EBI-367390,EBI-10243107

Protein-protein interaction databases

BioGridi123689. 41 interactors.
DIPiDIP-32490N.
IntActiQ8WWW0. 44 interactors.
STRINGi9606.ENSP00000347443.

Structurei

Secondary structure

1418
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi369 – 371Combined sources3
Helixi374 – 411Combined sources38

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LGDX-ray3.05E/F/G/H365-413[»]
4OH8X-ray2.28B366-418[»]
ProteinModelPortaliQ8WWW0.
SMRiQ8WWW0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini274 – 364Ras-associatingPROSITE-ProRule annotationAdd BLAST91
Domaini366 – 413SARAHPROSITE-ProRule annotationAdd BLAST48

Sequence similaritiesi

Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 Ras-associating domain.PROSITE-ProRule annotation
Contains 1 SARAH domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri122 – 170Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST49

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IPAE. Eukaryota.
ENOG4111HS2. LUCA.
GeneTreeiENSGT00390000003367.
HOGENOMiHOG000013025.
HOVERGENiHBG054362.
InParanoidiQ8WWW0.
KOiK08015.
OMAiMTIGSSM.
OrthoDBiEOG091G0EPB.
PhylomeDBiQ8WWW0.
TreeFamiTF319243.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR033614. C-RASSF.
IPR002219. PE/DAG-bd.
IPR000159. RA_dom.
IPR033623. RASSF5.
IPR011524. SARAH_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR22738. PTHR22738. 1 hit.
PTHR22738:SF9. PTHR22738:SF9. 1 hit.
PfamiPF00130. C1_1. 1 hit.
PF16517. Nore1-SARAH. 1 hit.
PF00788. RA. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00314. RA. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS50200. RA. 1 hit.
PS50951. SARAH. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WWW0-1) [UniParc]FASTAAdd to basket
Also known as: A, NORE1A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAMASPAIGQ RPYPLLLDPE PPRYLQSLSG PELPPPPPDR SSRLCVPAPL
60 70 80 90 100
STAPGAREGR SARRAARGNL EPPPRASRPA RPLRPGLQQR LRRRPGAPRP
110 120 130 140 150
RDVRSIFEQP QDPRVPAERG EGHCFAELVL PGGPGWCDLC GREVLRQALR
160 170 180 190 200
CTNCKFTCHP ECRSLIQLDC SQQEGLSRDR PSPESTLTVT FSQNVCKPVE
210 220 230 240 250
ETQRPPTLQE IKQKIDSYNT REKNCLGMKL SEDGTYTGFI KVHLKLRRPV
260 270 280 290 300
TVPAGIRPQS IYDAIKEVNL AATTDKRTSF YLPLDAIKQL HISSTTTVSE
310 320 330 340 350
VIQGLLKKFM VVDNPQKFAL FKRIHKDGQV LFQKLSIADR PLYLRLLAGP
360 370 380 390 400
DTEVLSFVLK ENETGEVEWD AFSIPELQNF LTILEKEEQD KIQQVQKKYD
410
KFRQKLEEAL RESQGKPG
Length:418
Mass (Da):47,090
Last modified:March 1, 2002 - v1
Checksum:i4AFBC69B1325CC9E
GO
Isoform 2 (identifier: Q8WWW0-2) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     1-153: Missing.
     154-193: CKFTCHPECR...ESTLTVTFSQ → MTVDSSMSSG...RNAQSKHLSK

Show »
Length:265
Mass (Da):30,359
Checksum:i66AD5D84EFA6D6CB
GO
Isoform 3 (identifier: Q8WWW0-3) [UniParc]FASTAAdd to basket
Also known as: C, NORE1B

The sequence of this isoform differs from the canonical sequence as follows:
     331-336: LFQKLS → GCLLHP
     337-418: Missing.

Show »
Length:336
Mass (Da):37,433
Checksum:i2657B6DAECD8D6A9
GO

Sequence cautioni

The sequence AAH04270 differs from that shown. Aberrant splicing.Curated
The sequence AAH04270 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH07203 differs from that shown. Aberrant splicing.Curated
The sequence AAH07203 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0193631 – 153Missing in isoform 2. 5 PublicationsAdd BLAST153
Alternative sequenceiVSP_019364154 – 193CKFTC…VTFSQ → MTVDSSMSSGYCSLDEELED CFFTAKTTFFRNAQSKHLSK in isoform 2. 5 PublicationsAdd BLAST40
Alternative sequenceiVSP_019365331 – 336LFQKLS → GCLLHP in isoform 3. 1 Publication6
Alternative sequenceiVSP_019366337 – 418Missing in isoform 3. 1 PublicationAdd BLAST82

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF445801 mRNA. Translation: AAL38592.1.
AY261332 mRNA. Translation: AAP83360.1.
AY062002 mRNA. Translation: AAL40388.1.
AY062003 mRNA. Translation: AAL40389.1.
AY216268 mRNA. Translation: AAO61668.1.
AK289861 mRNA. Translation: BAF82550.1.
AL832784 mRNA. Translation: CAI46164.1.
AL591846, AL354681 Genomic DNA. Translation: CAI13536.1.
AL591846, AL354681 Genomic DNA. Translation: CAI13538.1.
AL354681, AL591846 Genomic DNA. Translation: CAI15252.1.
AL591846, AL354681 Genomic DNA. Translation: CAI13537.1.
AL591846, AL354681 Genomic DNA. Translation: CAI13542.1.
AL354681, AL591846 Genomic DNA. Translation: CAI15253.1.
AL354681, AL591846 Genomic DNA. Translation: CAI15254.1.
AL354681, AL591846 Genomic DNA. Translation: CAI15256.1.
CH471100 Genomic DNA. Translation: EAW93544.1.
BC004270 mRNA. Translation: AAH04270.1. Sequence problems.
BC007203 mRNA. Translation: AAH07203.1. Sequence problems.
BC042651 mRNA. Translation: AAH42651.1.
CCDSiCCDS1463.1. [Q8WWW0-3]
CCDS1464.1. [Q8WWW0-2]
CCDS30998.1. [Q8WWW0-1]
RefSeqiNP_872604.1. NM_182663.3. [Q8WWW0-1]
NP_872605.1. NM_182664.3. [Q8WWW0-3]
NP_872606.1. NM_182665.3. [Q8WWW0-2]
UniGeneiHs.497579.

Genome annotation databases

EnsembliENST00000577571; ENSP00000462576; ENSG00000266094. [Q8WWW0-2]
ENST00000579436; ENSP00000462099; ENSG00000266094. [Q8WWW0-1]
ENST00000580449; ENSP00000462544; ENSG00000266094. [Q8WWW0-3]
GeneIDi83593.
KEGGihsa:83593.
UCSCiuc031vlp.2. human. [Q8WWW0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF445801 mRNA. Translation: AAL38592.1.
AY261332 mRNA. Translation: AAP83360.1.
AY062002 mRNA. Translation: AAL40388.1.
AY062003 mRNA. Translation: AAL40389.1.
AY216268 mRNA. Translation: AAO61668.1.
AK289861 mRNA. Translation: BAF82550.1.
AL832784 mRNA. Translation: CAI46164.1.
AL591846, AL354681 Genomic DNA. Translation: CAI13536.1.
AL591846, AL354681 Genomic DNA. Translation: CAI13538.1.
AL354681, AL591846 Genomic DNA. Translation: CAI15252.1.
AL591846, AL354681 Genomic DNA. Translation: CAI13537.1.
AL591846, AL354681 Genomic DNA. Translation: CAI13542.1.
AL354681, AL591846 Genomic DNA. Translation: CAI15253.1.
AL354681, AL591846 Genomic DNA. Translation: CAI15254.1.
AL354681, AL591846 Genomic DNA. Translation: CAI15256.1.
CH471100 Genomic DNA. Translation: EAW93544.1.
BC004270 mRNA. Translation: AAH04270.1. Sequence problems.
BC007203 mRNA. Translation: AAH07203.1. Sequence problems.
BC042651 mRNA. Translation: AAH42651.1.
CCDSiCCDS1463.1. [Q8WWW0-3]
CCDS1464.1. [Q8WWW0-2]
CCDS30998.1. [Q8WWW0-1]
RefSeqiNP_872604.1. NM_182663.3. [Q8WWW0-1]
NP_872605.1. NM_182664.3. [Q8WWW0-3]
NP_872606.1. NM_182665.3. [Q8WWW0-2]
UniGeneiHs.497579.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LGDX-ray3.05E/F/G/H365-413[»]
4OH8X-ray2.28B366-418[»]
ProteinModelPortaliQ8WWW0.
SMRiQ8WWW0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123689. 41 interactors.
DIPiDIP-32490N.
IntActiQ8WWW0. 44 interactors.
STRINGi9606.ENSP00000347443.

PTM databases

iPTMnetiQ8WWW0.
PhosphoSitePlusiQ8WWW0.

Polymorphism and mutation databases

BioMutaiRASSF5.
DMDMi74751587.

Proteomic databases

EPDiQ8WWW0.
MaxQBiQ8WWW0.
PaxDbiQ8WWW0.
PeptideAtlasiQ8WWW0.
PRIDEiQ8WWW0.

Protocols and materials databases

DNASUi83593.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000577571; ENSP00000462576; ENSG00000266094. [Q8WWW0-2]
ENST00000579436; ENSP00000462099; ENSG00000266094. [Q8WWW0-1]
ENST00000580449; ENSP00000462544; ENSG00000266094. [Q8WWW0-3]
GeneIDi83593.
KEGGihsa:83593.
UCSCiuc031vlp.2. human. [Q8WWW0-1]

Organism-specific databases

CTDi83593.
DisGeNETi83593.
GeneCardsiRASSF5.
HGNCiHGNC:17609. RASSF5.
MIMi607020. gene.
neXtProtiNX_Q8WWW0.
OpenTargetsiENSG00000266094.
PharmGKBiPA134958571.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IPAE. Eukaryota.
ENOG4111HS2. LUCA.
GeneTreeiENSGT00390000003367.
HOGENOMiHOG000013025.
HOVERGENiHBG054362.
InParanoidiQ8WWW0.
KOiK08015.
OMAiMTIGSSM.
OrthoDBiEOG091G0EPB.
PhylomeDBiQ8WWW0.
TreeFamiTF319243.

Enzyme and pathway databases

SignaLinkiQ8WWW0.
SIGNORiQ8WWW0.

Miscellaneous databases

ChiTaRSiRASSF5. human.
GeneWikiiRASSF5.
GenomeRNAii83593.
PROiQ8WWW0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136653.
CleanExiHS_RASSF5.
ExpressionAtlasiQ8WWW0. baseline and differential.
GenevisibleiQ8WWW0. HS.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR033614. C-RASSF.
IPR002219. PE/DAG-bd.
IPR000159. RA_dom.
IPR033623. RASSF5.
IPR011524. SARAH_dom.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR22738. PTHR22738. 1 hit.
PTHR22738:SF9. PTHR22738:SF9. 1 hit.
PfamiPF00130. C1_1. 1 hit.
PF16517. Nore1-SARAH. 1 hit.
PF00788. RA. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM00314. RA. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS50200. RA. 1 hit.
PS50951. SARAH. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRASF5_HUMAN
AccessioniPrimary (citable) accession number: Q8WWW0
Secondary accession number(s): A8K1E6
, Q5SY32, Q8WWV9, Q8WXF4, Q9BT99
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: March 1, 2002
Last modified: November 30, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Was termed (Ref. 3) RASSF3.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.